Complement activation in vivo in cancer patients receiving C. parvum immunotherapy

Serum complement levels were assayed in 26 patients with disseminated cancer, who received immunotherapy with infusion of C. parvum. Complement activation, indicated by the consumption of C3 or C4 or both, was found in 46% of the patients. Serum samples showed direct correlation between decreased C3 and conversion of C3 proactivator, whereas such conversion did not occur when C4 alone was decreased. It is concluded that the bypass (properdin) pathway was activated in patients in whom C3 consumption was detected, while the classical (C1) pathway was activated in the patients with C4 consumption unaccompanied by C3 decrease. Direct correlation was observed between delayed cutaneous hypersensitivity reactions to recall antigens and the incidence of C. parvum-associated complement activation.     

Creatine kinase. Modification of the working enzyme

The action of amiodarone (1.5 X 10(-5) M) on sinus node activity of spontaneously beating isolated right atria of rabbit at 30 degrees C was investigated using a microelectrode technique. The drug significantly increased the action potential duration and decreased the slope of diastolic depolarization, both effects leading to a reduction of the sinus rate. In contrast to beta-blocking agents, amiodarone reduced but did not completely abolish the adrenergic effects on the sinus node activity. It is concluded that the amiodarone-induced bradycarida observed in clinical trials might be due to a direct effect of the drug on the sinus node.     

Phase I studies with Baker's Antifol (BAF) (NSC 139105)

Phase I studies were conducted in 58 adult cancer patients with Baker's Antifol (BAF), a new active-site directed inhibitor of dihydrofolate reductase. Dose escalation ranged from 10 to 250 mg/m2/day X 5 days and courses of treatment were repeated every 2-3 weeks. Biologic effects were observed mostly at doses greater than 100 mg/m2/day X 5 days. The patients developed myelosuppression during 19% of the trials. Other types of toxicity were dermatitis in 12 to 30% and stomatitis in 7 to 38% of the trials. Toxicity was directly related to the impairment of the patient's liver function. Two partial responses (in a patient with adenocarcinoma of the lung and a patient with transitional cell carcinoma of the bladder) occurred. BAF is an active new chemotherapeutic agent which deserves further clinical trials in patients with various malignancies.     

(Vinylaryloxy)acetic acids. A new class of diuretic agents. 3. ((2-Nitro-1-alkenyl)aryloxy)acetic acids

A series of [(2-nitro-1-alkenyl)aryloxy]acetic acids was synthesized and tested in dogs for saluretic and diuretic activity. A number of these compounds exhibit a high order of activity on iv or po administration; representative of these is (E)-[2,3-dichloro-4-(2-nitropropenyl)phenoxy]acetic acid (5). The most highly active compounds are qualitatively similar in action to [2,3-dichloro-4-(2-methylenebutyryl)phenoxylacetic acid (ethacrynic acid) in causing a prompt increase in the excretion of water and of sodium and chloride ions in approximately equimolar amounts but are three to five times as potent. Potassium ion excretion is increased but less markedly than sodium excretion.     

Rat intestinal brush border membrane peptidases. I. Solubilization, purification, and physicochemical properties of two different forms of the enzyme

Two brush border peptidases have been isolated from the particulate fraction of the rat intestinal mucosa and purified to homogeneity as judged by polyacrylamide gel electrophoresis, starch gel electrophoresis, isoelectric focusing, and double immunodiffusion. For convenience, the peptidases have been designated peptidase F (fast) and S (slow) on the basis of their anodic mobilities. The isoelectric point of peptidase F was 4.76 and of peptidase S, 5.10. Both enzymes are glycoproteins. The amino acid compositions of the two peptidases are similar. The same carbohydrates are found in both enzymes, but there are differences in the molar concentrations of individual sugars. Peptidase S has greater concentrations of mannose and galactose and of hexosamines than peptidase F, while sialic acid is slightly greater in peptidase F. Carbohydrate accounted for approximately 19% and 23% of the weight of peptidases F and S, respectively. Estimates of the molecular weights of both enzymes by gel filtration gave values of 280,000. Electrophoresis of the enzymes under denaturing conditions on sodium dodecyl sulfate polyacrylamide gels indicated that each enzyme is a dimer consisting of two subunits of equal molecular weight, 140,000.     

Chemotactic responses of normal human basophils to C5a and to lymphocyte-derived chemotactic factor

Peripheral blood basophils from normal human subjects responded chemotactically to the complement component C5a and also to the supernatant fluid from cultured human lymphocytes stimulated by mitogens or specific antigen. Basophil chemotactic factor (BCF) was detected in stimulated lymphocyte cultures within 24 hr and increased for the first 3 days. BCF was found after stimulation of lymphocytes by B or T cell mitogens as well as by specific antigen. The amount of BCF in culture fluids was independent of cell proliferation. Monocyte chemotactic factor (MCF) and BCF could not be separated from one another by Sephadex or DEAE chromatography. Both activities were eluted from Sephadex G-100 columns in a m.w. region of about 15,000 daltons and were found after ion exchange chromatography on DEAE in a peak eluted by 0.1 M NaCl. These findings suggest that mitogen or antigen-stimulated lymphocytes secrete a molecule that is chemotactic for both monocytes and basophils. Thus, in the absence of a basophil-specific chemotactic molecule, the preferential accumulation of basophils in certain types of delayed hypersensitivity skin reactions must be due to additional factors such as basophil chemotaxis augmentation factor.     

Spontaneous dissection of the internal carotid artery

The arteriographic diagnosis of spontaneous, nontraumatic dissection of the internal carotid artery was made in 19 patients and confirmed at operation in ten. The tapered narrowing beginning in or about the carotid bulb and ending at the bony canal was a consistent finding. Four patients had associated aneurysm formation. All but one patient developed an acute hemispheric neurologic deficit as the initial symptom. The deficit was transient in ten and prolonged in eight. The dissection occurred in the outer layers of the media. None of the surgical specimens showed atherosclerosis. Surgical methods of management included segmental resection and grafting, thrombectomy and intimectomy, dilation, and simple ligation. Considerable improvement of luminal diameter occurred in six of seven patients whose arteries were left undisturbed.